|
|
 Previous Article | Table of Contents | Next Article 
A Randomized, Double-Blind, Placebo-Controlled, Phase III Study of Filgrastim in Remission Induction and Consolidation Therapy for Adults With De Novo Acute Myeloid Leukemia
Gerhard Heil,
Dieter Hoelzer,
Miguel A. Sanz,
Klaus Lechner,
John A. Liu Yin,
Giuseppe Papa,
Luc Noens,
Jeff Szer,
Arnold Ganser,
Caroline O'Brien,
James Matcham, and
Alan Barge for The International Acute Myeloid Leukemia Study Group
From the University of Ulm, Ulm, Germany; the University of Frankfurt, Frankfurt, Germany; La Fe Hospital, Valencia, Spain; the University of Vienna, Vienna, Austria; Manchester Royal Infirmary, Manchester, UK; the University of Rome, Rome, Italy; the University of Gent, Ghent, Belgium; Royal Melbourne Hospital, Melbourne, Australia; and Amgen Ltd, Cambridge, UK.
The safety and efficacy of filgrastim as an adjunct to acute myeloid leukemia (AML) induction and consolidation therapy was assessed in this prospective double-blind, randomized, placebo-controlled, multicenter trial. A total of 521 consecutive de novo AML patients aged 16 or more years were randomized to receive filgrastim (5 µg/kg/d subcutaneously) or placebo after standard induction as well as consolidation chemotherapy. Blinded study drug was given from 24 hours after chemotherapy until the absolute neutrophil count was  1.0 × 109/L for 3 consecutive days. The overall complete remission rate was 68%. After a median follow-up of 24 months (range 5 to 40) the median disease-free survival was 10 months (95% confidence interval [CI], 8.7 to 10.8) and the median overall survival was 13 months (95%CI, 12.2 to 14.6). These did not differ between treatment groups. Patients receiving filgrastim experienced neutrophil recovery 5 days earlier after induction 1 than those receiving placebo (P < .0001). This was accompanied by reductions in the duration of fever (7 v 8.5 days; P = .009), parenteral antibiotic use (15 v 18.5 days; P = .0001), and hospitalization (20 v 25 days; P = .0001). Similar reductions were seen after induction 2 and the consolidation courses. There was a significant reduction in the number of patients requiring systemic antifungal therapy in the filgrastim group during induction treatment (34% v 43%; P = .04). In conclusion, filgrastim is safe in that it had no negative impact on the prognosis of the AML patients. In addition, it effectively reduced the duration of neutropenia, leading to significant clinical benefits by reducing the duration of fever; requirement for parenteral anti-infectives, specifically amphotericin B; and the duration of hospitalization.
Blood, Vol. 90 No. 12 (December 15), 1997:
pp. 4710-4718
© 1997 by The American Society of Hematology.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
E. Morra, G. Barosi, A. Bosi, F. Ferrara, F. Locatelli, M. Marchetti, G. Martinelli, C. Mecucci, M. Vignetti, and S. Tura
Clinical management of primary non-acute promyelocytic leukemia acute myeloid leukemia: practice Guidelines by the Italian Society of Hematology, the Italian Society of Experimental Hematology and the Italian Group for Bone Marrow Transplantation
Haematologica,
January 1, 2009;
94(1):
102 - 112.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Maurillo, F. Buccisano, M. I. Del Principe, G. Del Poeta, A. Spagnoli, P. Panetta, E. Ammatuna, B. Neri, L. Ottaviani, C. Sarlo, et al.
Toward Optimization of Postremission Therapy for Residual Disease-Positive Patients With Acute Myeloid Leukemia
J. Clin. Oncol.,
October 20, 2008;
26(30):
4944 - 4951.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. von Lilienfeld-Toal, C. Hahn-Ast, H. Kirchner, D. Flieger, G. Dolken, and A. Glasmacher
A randomized comparison of immediate versus delayed application of G-CSF in induction therapy for patients with acute myeloid leukemia unfit for intensive chemotherapy
Haematologica,
December 1, 2007;
92(12):
1719 - 1720.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Ozer, B. Mirtsching, M. Rader, S. Luedke, S. J. Noga, B. Ding, and L. Dreiling
In Reply
Oncologist,
December 1, 2007;
12(12):
1465 - 1466.
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Sung, P. C. Nathan, S. M.H. Alibhai, G. A. Tomlinson, and J. Beyene
Meta-analysis: Effect of Prophylactic Hematopoietic Colony-Stimulating Factors on Mortality and Outcomes of Infection
Ann Intern Med,
September 18, 2007;
147(6):
400 - 411.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. L. Speshock, N. Doyon-Reale, R. Rabah, M. N. Neely, and P. C. Roberts
Filamentous Influenza A Virus Infection Predisposes Mice to Fatal Septicemia following Superinfection with Streptococcus pneumoniae Serotype 3
Infect. Immun.,
June 1, 2007;
75(6):
3102 - 3111.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Maurillo, F. Buccisano, A. Spagnoli, G. Del Poeta, P. Panetta, B. Neri, M. I. Del Principe, C. Mazzone, M. I. Consalvo, A. Tamburini, et al.
Monitoring of minimal residual disease in adult acute myeloid leukemia using peripheral blood as an alternative source to bone marrow
Haematologica,
May 1, 2007;
92(5):
605 - 611.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Hershman, A. I. Neugut, J. S. Jacobson, J. Wang, W.-Y. Tsai, R. McBride, C. L. Bennett, and V. R. Grann
Acute Myeloid Leukemia or Myelodysplastic Syndrome Following Use of Granulocyte Colony-Stimulating Factors During Breast Cancer Adjuvant Chemotherapy
J Natl Cancer Inst,
February 7, 2007;
99(3):
196 - 205.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. M. Shammo and F. M. Stewart
Hematopoietic growth factors
ASH Self-Assessment Program,
January 1, 2007;
2007(1):
45 - 60.
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. J. Smith, J. Khatcheressian, G. H. Lyman, H. Ozer, J. O. Armitage, L. Balducci, C. L. Bennett, S. B. Cantor, J. Crawford, S. J. Cross, et al.
2006 Update of Recommendations for the Use of White Blood Cell Growth Factors: An Evidence-Based Clinical Practice Guideline
J. Clin. Oncol.,
July 1, 2006;
24(19):
3187 - 3205.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. W. Milligan, K. Wheatley, T. Littlewood, J. I. O. Craig, A. K. Burnett, and for the NCRI Haematological Oncology Clinical Stud
Fludarabine and cytosine are less effective than standard ADE chemotherapy in high-risk acute myeloid leukemia, and addition of G-CSF and ATRA are not beneficial: results of the MRC AML-HR randomized trial
Blood,
June 15, 2006;
107(12):
4614 - 4622.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Weycker, J. Hackett, J. S Edelsberg, G. Oster, and A. G Glass
Are Shorter Courses of Filgrastim Prophylaxis Associated with Increased Risk of Hospitalization?
Ann. Pharmacother.,
March 1, 2006;
40(3):
402 - 407.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. J. Jabbour, E. Estey, and H. M. Kantarjian
Adult Acute Myeloid Leukemia
Mayo Clin. Proc.,
February 1, 2006;
81(2):
247 - 260.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. N. Timmer-Bonte, T. M. de Boo, H. J. Smit, B. Biesma, F. A. Wilschut, S. A. Cheragwandi, A. Termeer, C. A. Hensing, J. Akkermans, E. M. Adang, et al.
Prevention of Chemotherapy-Induced Febrile Neutropenia by Prophylactic Antibiotics Plus or Minus Granulocyte Colony-Stimulating Factor in Small-Cell Lung Cancer: A Dutch Randomized Phase III Study
J. Clin. Oncol.,
November 1, 2005;
23(31):
7974 - 7984.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Amadori, S. Suciu, U. Jehn, R. Stasi, X. Thomas, J.-P. Marie, P. Muus, F. Lefrere, Z. Berneman, G. Fillet, et al.
Use of glycosylated recombinant human G-CSF (lenograstim) during and/or after induction chemotherapy in patients 61 years of age and older with acute myeloid leukemia: final results of AML-13, a randomized phase-3 study
Blood,
July 1, 2005;
106(1):
27 - 34.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. M. Stull, R. Bilmes, H. Kim, and R. Fichtl
Comparison of sargramostim and filgrastim in the treatment of chemotherapy-induced neutropenia
Am. J. Health Syst. Pharm.,
January 1, 2005;
62(1):
83 - 87.
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. M. Rowe, D. Neuberg, W. Friedenberg, J. M. Bennett, E. Paietta, A. Z. Makary, J. L. Liesveld, C. N. Abboud, G. Dewald, F. A. Hayes, et al.
A phase 3 study of three induction regimens and of priming with GM-CSF in older adults with acute myeloid leukemia: a trial by the Eastern Cooperative Oncology Group
Blood,
January 15, 2004;
103(2):
479 - 485.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. L Stanford, S. D Zondor, and E. Cobos
Is pegfilgrastim appropriate for the treatment of established febrile neutropenia?
Journal of Oncology Pharmacy Practice,
June 1, 2003;
9(2-3):
113 - 119.
[Abstract]
[PDF]
|
|
|
|
|
|
|
M. V. Relling, J. M. Boyett, J. G. Blanco, S. Raimondi, F. G. Behm, J. T. Sandlund, G. K. Rivera, L. E. Kun, W. E. Evans, and C.-H. Pui
Granulocyte colony-stimulating factor and the risk of secondary myeloid malignancy after etoposide treatment
Blood,
May 15, 2003;
101(10):
3862 - 3867.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. D. Green, H. Koelbl, J. Baselga, A. Galid, V. Guillem, P. Gascon, S. Siena, R. I. Lalisang, H. Samonigg, M. R. Clemens, et al.
A randomized double-blind multicenter phase III study of fixed-dose single-administration pegfilgrastim versus daily filgrastim in patients receiving myelosuppressive chemotherapy
Ann. Onc.,
January 1, 2003;
14(1):
29 - 35.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. M. Stone
The Difficult Problem of Acute Myeloid Leukemia in the Older Adult
CA Cancer J Clin,
November 1, 2002;
52(6):
363 - 371.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. K. Ellis, R. B. Livingston, J. R. Gralow, S. J. Green, and T. Thompson
Dose-Dense Anthracycline-Based Chemotherapy for Node-Positive Breast Cancer
J. Clin. Oncol.,
September 1, 2002;
20(17):
3637 - 3643.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Menzin, K. Lang, C. C. Earle, D. Kerney, and R. Mallick
The Outcomes and Costs of Acute Myeloid Leukemia Among the Elderly
Arch Intern Med,
July 22, 2002;
162(14):
1597 - 1603.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. M. Stone, D. T. Berg, S. L. George, R. K. Dodge, P. A. Paciucci, P. P. Schulman, E. J. Lee, J. O. Moore, B. L. Powell, M. R. Baer, et al.
Postremission therapy in older patients with de novo acute myeloid leukemia: a randomized trial comparing mitoxantrone and intermediate-dose cytarabine with standard-dose cytarabine
Blood,
August 1, 2001;
98(3):
548 - 553.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Balducci, G. H. Lyman, and H. Ozer
Patients Aged {>=} 70 Are at High Risk for Neutropenic Infection and Should Receive Hemopoietic Growth Factors When Treated With Moderately Toxic Chemotherapy
J. Clin. Oncol.,
March 1, 2001;
19(5):
1583 - 1585.
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Venditti, F. Buccisano, G. Del Poeta, L. Maurillo, A. Tamburini, C. Cox, A. Battaglia, G. Catalano, B. Del Moro, L. Cudillo, et al.
Level of minimal residual disease after consolidation therapy predicts outcome in acute myeloid leukemia
Blood,
December 1, 2000;
96(12):
3948 - 3952.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Ozer, J. O. Armitage, C. L. Bennett, J. Crawford, G. D. Demetri, P. A. Pizzo, C. A. Schiffer, T. J. Smith, G. Somlo, J. C. Wade, et al.
2000 Update of Recommendations for the Use of Hematopoietic Colony-Stimulating Factors: Evidence-Based, Clinical Practice Guidelines
J. Clin. Oncol.,
October 20, 2000;
18(20):
3558 - 3585.
[Full Text]
[PDF]
|
|
|
|
|
|
|
O. Bruserud, G. Tjønnfjord, B. T. Gjertsen, B. Foss, and P. Ernst
New Strategies in the Treatment of Acute Myelogenous Leukemia: Mobilization and Transplantation of Autologous Peripheral Blood Stem Cells in Adult Patients
Stem Cells,
September 1, 2000;
18(5):
343 - 351.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
C. A. Schiffer, K. Miller, R. A. Larson, P. C. Amrein, J. H. Antin, V. J. Zani, and R. M. Stone
A double-blind, placebo-controlled trial of pegylated recombinant human megakaryocyte growth and development factor as an adjunct to induction and consolidation therapy for patients with acute myeloid leukemia
Blood,
April 15, 2000;
95(8):
2530 - 2535.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. L. Harousseau, B. Witz, B. Lioure, M. Hunault-Berger, B. Desablens, M. Delain, F. Guilhot, P. Y. Le Prise, J. F. Abgrall, E. Deconinck, et al.
Granulocyte Colony-Stimulating Factor After Intensive Consolidation Chemotherapy in Acute Myeloid Leukemia: Results of a Randomized Trial of the Groupe Ouest-Est Leucemies Aigues Myeloblastiques
J. Clin. Oncol.,
February 14, 2000;
18(4):
780 - 780.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Archimbaud, O. G. Ottmann, J. A. L. Yin, K. Lechner, H. Dombret, M. A. Sanz, G. Heil, P. Fenaux, W. Brugger, A. Barge, et al.
A Randomized, Double-Blind, Placebo-Controlled Study With Pegylated Recombinant Human Megakaryocyte Growth and Development Factor (PEG-rHuMGDF) as an Adjunct to Chemotherapy for Adults With De Novo Acute Myeloid Leukemia
Blood,
December 1, 1999;
94(11):
3694 - 3701.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. Hiddemann, W. Kern, C. Schoch, C. Fonatsch, A. Heinecke, B. Wormann, and T. Buchner
Management of Acute Myeloid Leukemia in Elderly Patients
J. Clin. Oncol.,
November 1, 1999;
17(11):
3569 - 3576.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Lowenberg, J. R. Downing, and A. Burnett
Acute Myeloid Leukemia
N. Engl. J. Med.,
September 30, 1999;
341(14):
1051 - 1062.
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. H. Estey, P. F. Thall, S. Pierce, J. Cortes, M. Beran, H. Kantarjian, M. J. Keating, M. Andreeff, and E. Freireich
Randomized Phase II Study of Fludarabine + Cytosine Arabinoside + Idarubicin ± All-Trans Retinoic Acid ± Granulocyte Colony-Stimulating Factor in Poor Prognosis Newly Diagnosed Acute Myeloid Leukemia and Myelodysplastic Syndrome
Blood,
April 15, 1999;
93(8):
2478 - 2484.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. E. Godwin, K. J. Kopecky, D. R. Head, C. L. Willman, C. P. Leith, H. E. Hynes, S. P. Balcerzak, and F. R. Appelbaum
A Double-Blind Placebo-Controlled Trial of Granulocyte Colony-Stimulating Factor in Elderly Patients With Previously Untreated Acute Myeloid Leukemia: A Southwest Oncology Group Study (9031)
Blood,
May 15, 1998;
91(10):
3607 - 3615.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
